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Described herein are methods for increasing the ion permeability of a
silicone hydrogel contact lens by adding a small amount of an
ion-permeability-enhancing ("IP-enhancing") hydrophilic vinylic monomer
or macromer into a lens-forming material for cast-molding silicone
hydrogel contact lenses, while not altering significantly the water
content and/or the oxygen permeability of resultant lenses from the
lens-forming material.

Inventors:

Qiu; Yongxing; (Duluth, GA); Qian; Xinming; (Johns Creek, GA)

Serial No.:

960612

Series Code:

12

Filed:

December 6, 2010

Current U.S. Class:

264/1.1

Class at Publication:

264/1.1

International Class:

B29D 11/00 20060101 B29D011/00

Claims

1. A method for increasing the ion permeability of a silicone hydrogel
contact lens, the method comprising: a. introducing into a mold a
lens-forming material, wherein the lens-forming material comprises (i) at
least one silicone-containing vinylic monomer or macromer, (ii) at least
one hydrophilic vinylic monomer; and (iii) at least one IP-enhancing
vinylic monomer or macromer represented by formula I; ##STR00008##
wherein X.sup.1 is a direct bond, an oxygen atom ##STR00009## wherein
R' is H or C.sub.1-C.sub.4 alkyl; L is a direct bond, a linear or
branched C.sub.1-C.sub.10 alkylene divalent radical, or a divalent
radical of --X.sup.3-E-X.sup.4--, wherein X.sup.3 and X.sup.4 are,
independently, a linkage selected from the group consisting of
##STR00010## E is an alkylene divalent radical, a cycloalkyl diradical,
an alkylcycloalkyl diradical, an alkylaryl diradical, or an aryl
diradical with up to 40 carbon atoms, wherein E optionally can have
ether, thio, or amine linkages in the main chain; Y is
--(R.sup.1--O).sub.n--(R.sup.2--O).sub.m--(R.sup.3--O).sub.p--R, wherein
R.sup.1, R.sup.2, and R.sup.3 are, independently, a linear or branched
C.sub.2-C.sub.4-alkylene; n, m and p are, independently, a number from 0
to 100, wherein the sum of (n+m+p) is 2 to 100; and R is hydrogen, a
C.sub.1-C.sub.4 alkyl or alkoxy radical; and Z is hydrogen or methyl. b.
curing the lens-forming mixture to produce the lens; and c. removing the
lens from the mold, wherein the IP-enhancing vinylic monomer is present
up to 3% by weight and is sufficient to provide the resultant lens with
an increased ion permeability compared to a control lens while not
significantly altering the water content and the oxygen permeability of
the resultant lens.

2. The method of claim 1, wherein the lens has an ion permeability that
is at least 40% greater than the control lens.

4. The method of claim 1, wherein Y comprises a polyalkylene oxide having
a molecular weight of about 100 to 10,000.

5. The method of claim 1, wherein Y comprises a residue of polyethylene
glycol having a molecular weight of 500 to 2,500, and Z is methyl.

6. The method of claim 1, wherein there are two different compounds
having the formula I, wherein for each compound Y comprises a residue of
polyethylene glycol having a molecular weight of 500 to 2,500, wherein
the molecular weight of the polyethylene glycol residue for each compound
is different.

9. The method of claim 1, wherein the hydrophilic vinylic monomer
comprises a hydroxyl-substituted lower alkyl (C.sub.1 to C.sub.3)
(meth)acrylate, a hydroxyl-substituted lower alkyl vinyl ether, a C.sub.1
to C.sub.3 alkyl(meth)acrylamide, a di-(C.sub.1-C.sub.3
alkyl)(meth)acrylamide, an N-vinylpyrrole, an N-vinyl-2-pyrrolidone, a
2-vinyloxazoline, a 2-vinyl-4,4'-dialkyloxazolin-5-one, a 2- and
4-vinylpyridine, amino(lower alkyl), a mono(lower alkylamino)(lower
alkyl) and di(lower alkylamino)(lower alkyl)(meth)acrylate, an allyl
alcohol, an N-vinyl C.sub.1 to C.sub.3 alkylamide, an N-vinyl-N--C.sub.1
to C.sub.3 alkylamide, or any combination thereof.

15. The method of claim 1, wherein the lens-forming material further
comprises a polymerization initiator, a UV-absorber, a tinting agent, an
antimicrobial agent, an inhibitor, a filler, or any combination thereof.

[0002] This invention is related to a method for making silicone hydrogel
contact lenses with increased ion permeability.

BACKGROUND

[0003] In recent years, soft silicone hydrogel contact lenses have become
more and more popular because of their high oxygen permeability and
comfort. By having a high oxygen permeability, a silicone hydrogel
contact lens allows sufficient oxygen to permeate through the lens to the
cornea with minimal adverse effects on corneal health. In addition to
high oxygen permeability, on-eye movement of the lens is also required to
ensure good tear exchange, and ultimately, to ensure good corneal health.
Ion permeability is one of the predictors of on-eye movement, because the
permeability of ions is believed to be directly proportional to the
permeability of water. The methods described herein produce ophthalmic
lenses having improved ion permeability without adversely affecting other
properties of the lens.

SUMMARY

[0004] Described herein are methods for increasing the ion permeability of
an ophthalmic lens by adding a small amount of an
ion-permeability-enhancing ("IP-enhancing") hydrophilic vinylic monomer
or macromer into a lens-forming material for cast-molding silicone
hydrogel contact lenses, wherein the IP-enhancing vinylic monomer or
macromer is represented by formula I;

##STR00001##

[0005] wherein X.sup.1 is a direct bond, an oxygen atom

##STR00002##

wherein R' is H or C.sub.1-C.sub.4 alkyl;

[0006] L is a direct bond, a linear or branched C.sub.1-C.sub.10 alkylene
divalent radical (or so-called divalent aliphatic hydrocarbon radical),
or a divalent radical of --X.sup.3-E-X.sup.4--, wherein X.sup.3 and
X.sup.4 are, independently, a linkage selected from the group consisting
of

##STR00003##

[0007] E is an alkylene divalent radical, a cycloalkyl diradical, an
alkylcycloalkyl diradical, an alkylaryl diradical, or an aryl diradical
with up to 40 carbon atoms, wherein E optionally can have ether, thio, or
amine linkages in the main chain;

[0008] Y is
--(R.sup.1--O).sub.n--(R.sup.2--O).sub.m--(R.sup.3--O).sub.p--R, wherein
R.sup.1, R.sup.2, and R.sup.3 are, independently, a linear or branched
C.sub.2-C.sub.4-alkylene, and n, m and p are, independently, a number
from 0 to 100, wherein the sum of (n+m+p) is 2 to 100, and R is hydrogen,
a C.sub.1-C.sub.4 alkyl or alkoxy radical, and

[0009] Z is hydrogen or methyl.

[0010] In accordance with the invention, a lens is obtained by curing the
lens-forming material in a mold to form the lens and removing the lens
from the mold. The resultant lens has an increased ion permeability
compared to a control lens produced from a lens-forming material having
identical composition except without the IP-enhancing vinylic monomer or
macromer of the formula I. The advantages of the invention will be set
forth in part in the description which follows, and in part will be
obvious from the description, or may be learned by practice of the
aspects described below. The advantages described below will be realized
and attained by means of the elements and combinations particularly
pointed out in the appended claims. It is to be understood that both the
foregoing general description and the following detailed description are
exemplary and explanatory only and are not restrictive.

DETAILED DESCRIPTION

[0011] Before the ophthalmic lenses and methods are disclosed and
described, it is to be understood that the aspects described below are
not limited to specific compounds, synthetic methods, or uses as such
may, of course, vary. It is also to be understood that the terminology
used herein is for the purpose of describing particular aspects only and
is not intended to be limiting.

[0012] In this specification and in the claims that follow, reference will
be made to a number of terms that shall be defined to have the following
meanings:

[0013] It must be noted that, as used in the specification and the
appended claims, the singular forms "a," "an" and "the" include plural
referents unless the context clearly dictates otherwise. Thus, for
example, reference to "a monomer" includes mixtures of two or more such
monomers, and the like.

[0014] "Optional" or "optionally" means that the subsequently described
event or circumstance can or cannot occur, and that the description
includes instances where the event or circumstance occurs and instances
where it does not. For example, the phrase "optional tinting agent" means
that the tinting agent can or cannot be present.

[0015] Unless defined otherwise, all technical and scientific terms used
herein have the same meaning as commonly understood by one of ordinary
skill in the art to which this invention belongs. As employed throughout
the disclosure, the following terms, unless otherwise indicated, shall be
understood to have the following meanings.

[0016] The term "alkyl" as used herein is a branched or unbranched
saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl,
ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl,
heptyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl and the
like. A "lower alkyl" group is an alkyl group containing from one to six
carbon atoms.

[0017] The term "amino group" as used herein has the formula --NRR', where
R and R' are, independently, hydrogen, an alkyl group, or an aryl group.

[0018] The term "alkylene" as used herein refers to a divalent radical of
hydrocarbon.

[0019] The term "cycloalkyl group" as used herein is a non-aromatic
carbon-based ring composed of at least three carbon atoms. Examples of
cycloalkyl groups include, but are not limited to, cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, etc. The term "heterocycloalkyl
group" is a cycloalkyl group as defined above where at least one of the
carbon atoms of the ring is substituted with a heteroatom such as, but
not limited to, nitrogen, oxygen, sulphur, or phosphorus. The cycloalkyl
group can be substituted or unsubstituted. The cycloalkyl group can be
substituted with one or more groups including, but not limited to, alkyl,
alkynyl, alkenyl, aryl, halide, nitro, amino, ester, ketone, aldehyde,
hydroxy, carboxylic acid, or alkoxy.

[0020] The term "aryl" as used herein is any carbon-based aromatic group
including, but not limited to, benzene, naphthalene, etc. The term
"aromatic" also includes "heteroaryl group," which is defined as an
aromatic group that has at least one heteroatom incorporated within the
ring of the aromatic group. Examples of heteroatoms include, but are not
limited to, nitrogen, oxygen, sulfur, and phosphorus. The aryl group can
be substituted or unsubstituted. The aryl group can be substituted with
one or more groups including, but not limited to, alkyl, alkynyl,
alkenyl, aryl, halide, nitro, amino, ester, ketone, aldehyde, hydroxy,
carboxylic acid, or alkoxy.

[0021] The term "alkylene oxide" as used herein is a group composed of one
or more repeat units having the formula --(R.sup.a).sub.nO--, where
R.sup.a is a linear or branched C.sub.1-C.sub.4-alkylene and n is from 1
to 10.

[0022] The term "alkylene amine" as used herein is a group composed of one
or more repeat units having the formula --(R.sup.a).sub.nNR--, where
R.sup.a is a linear or branched C.sub.1-C.sub.4-alkylene, n is from 1 to
10, and R is hydrogen, an alkyl group, or an aryl group.

[0023] The term "carbonyl" as used herein is a group or molecule composed
of a C.dbd.O group. The carbonyl group can be present as an aldehyde,
ketone, ester, anhydride, or carboxylic acid group.

[0024] The term "dicarbonyl" as used herein is a group or molecule
composed of two C.dbd.O groups. Each carbonyl group, independently, can
be present as an aldehyde, ketone, ester, anhydride, or carboxylic acid
group.

[0025] The term "silicon group" as used herein is a group or molecule
composed of at least one silicon atom. The silicon group can be
substituted with one or more alkyl groups, where the alkyl groups can be
the same or different.

[0026] A "hydrogel" refers to a polymeric material that can absorb at
least 10 percent by weight of water when it is fully hydrated. A hydrogel
material can be obtained by polymerization or copolymerization of at
least one hydrophilic monomer in the presence of or in the absence of
additional monomers and/or macromers or by crosslinking of a prepolymer.

[0027] A "silicone hydrogel" refers to a hydrogel obtained by
copolymerization of a polymerizable composition comprising at least one
silicone-containing vinylic monomer or at least one silicone-containing
macromer or a silicone-containing prepolymer.

[0028] "Hydrophilic," as used herein, describes a material or portion
thereof that will more readily associate with water than with lipids.

[0029] The term "fluid" as used herein indicates that a material is
capable of flowing like a liquid.

[0030] As used herein, "actinically" in reference to curing or
polymerizing of a polymerizable composition or material means that the
curing (e.g., crosslinked and/or polymerized) is performed by actinic
irradiation, such as, for example, UV irradiation, ionized radiation
(e.g., gamma ray or X-ray irradiation), microwave irradiation, and the
like. Thermal curing or actinic curing methods are well-known to a person
skilled in the art.

[0031] A "monomer" means a low molecular weight compound that can be
polymerized actinically, thermally, or chemically. Low molecular weight
typically means average molecular weights less than 700 Daltons.

[0032] A "vinylic monomer," as used herein, refers to a low molecular
weight compound that has an ethylenically unsaturated group and can be
polymerized actinically, chemically or thermally. Low molecular weight
typically means average molecular weights less than 700 Daltons.

[0033] The term "olefinically unsaturated group" is employed herein in a
broad sense and is intended to encompass any groups containing at least
one >C.dbd..dbd.C< group. Exemplary ethylenically unsaturated
groups include without limitation acryloyl, methacryloyl, allyl, vinyl,
styrenyl, or other C.dbd.C containing groups.

[0034] A "hydrophilic vinylic monomer," as used herein, refers to a
vinylic monomer that is capable of forming a homopolymer that is water
soluble or can absorb at least 10 percent by weight water when fully
hydrated.

[0035] A "macromer" refers to a medium to high molecular weight compound
or polymer that contains functional groups capable of undergoing further
polymerizing/crosslinking reactions. Medium and high molecular weight
typically means average molecular weights greater than 700 Daltons. In
one aspect, the macromer contains ethylenically unsaturated groups and
can be polymerized actinically or thermally.

[0036] A "prepolymer" refers to a starting polymer that can be cured
(e.g., crosslinked and/or polymerized) actinically or thermally or
chemically to obtain a crosslinked and/or polymerized polymer having a
molecular weight much higher than the starting polymer. An
"actinically-crosslinkable prepolymer" refers to a starting polymer which
can be crosslinked upon actinic radiation or heating to obtain a
crosslinked polymer having a molecular weight much higher than the
starting polymer.

[0039] "Thermal initiator" refers to a chemical that initiates radical
crosslinking and/or polymerizing reaction by the use of heat energy.
Examples of suitable thermal initiators include, but are not limited to,
2,2'-azobis(2,4-dimethylpentanenitrile),
2,2'-azobis(2-methylpropanenitrile), 2,2'-azobis(2-mehylbutanenitrile),
peroxides such as benzoyl peroxide, and the like. In some aspects, the
thermal initiator is azobisisobutyronitrile (AIBN).

[0040] "Tinting agent," as used herein includes, but is not limited to, a
dye or a pigment that can be incorporated into the lens or lens forming
material.

[0041] An "antimicrobial agent" refers to a chemical that is capable of
decreasing or eliminating or inhibiting the growth of microorganisms such
as that term is known in the art.

[0042] "Surface modification" or "surface treatment", as used herein,
means that an article has been treated in a surface treatment process (or
a surface modification process) prior to or posterior to the formation of
the article, in which (1) a coating is applied to the surface of the
article, (2) chemical species are adsorbed onto the surface of the
article, (3) the chemical nature (e.g., electrostatic charge) of chemical
groups on the surface of the article are altered, or (4) the surface
properties of the article are otherwise modified. Exemplary surface
treatment processes include, but are not limited to, a surface treatment
by energy (e.g., a plasma, a static electrical charge, irradiation, or
other energy source), chemical treatments, the grafting of hydrophilic
monomers or macromers onto the surface of an article, mold-transfer
coating process disclosed in U.S. Pat. No. 6,719,929 (herein incorporated
by reference in its entirety), the incorporation of wetting agents into a
lens formulation for making contact lenses proposed in U.S. Pat. Nos.
6,367,929 and 6,822,016 (herein incorporated by references in their
entireties), reinforced mold-transfer coating disclosed in U.S. Patent
Application No. 60/811,949 (herein incorporated by reference in its
entirety), and LbL coating. A preferred class of surface treatment
processes is plasma processes, in which an ionized gas is applied to the
surface of an article. Plasma gases and processing conditions are
described more fully in U.S. Pat. Nos. 4,312,575 and 4,632,844, which are
incorporated herein by reference. The plasma gas is preferably a mixture
of lower alkanes and nitrogen, oxygen or an inert gas.

[0043] "Ophthalmic lens," as used herein, refers to a lens used on or
about the eye or the ocular vicinity. Examples of ophthalmic lenses
include, but are not limited to, contact lens (hard or soft), an
intraocular lens, a corneal onlay, or other lenses that are used on or
about the eye or the ocular vicinity.

[0044] "Contact lens" refers to a structure that can be placed on or
within a wearer's eye. A contact lens can correct, improve, or alter a
user's eyesight, but that need not be the case. A contact lens can be of
any appropriate material known in the art or later developed, and can be
a soft lens, a hard lens, or a hybrid lens. Typically a contact lens has
an anterior surface and an opposite posterior surface and a
circumferential edge where the anterior and posterior surfaces are
tapered off

[0045] "Water content" is the percentage by weight of water in a contact
lens when it is fully hydrated. The water content (%) of contact lenses
is measured using an ATAGO CL-1 Refractometer or an ATAGO N2-E
Refractometer.

[0046] The intrinsic "oxygen permeability" (Dk) of a material is the rate
at which oxygen will pass through a material. In accordance with the
invention, the term "oxygen permeability (Dk)" in reference to a material
or a contact lens means an apparent oxygen permeability which is measured
with a sample (film or lens) of 90 or 100 microns in average thickness
over the area being measured according to a coulometric method described
in Examples. Oxygen permeability is conventionally expressed in units of
barrers, where "barrer" is defined as [(cm.sup.3
oxygen)(mm)/(cm.sup.2)(sec)(mm Hg)].times.10.sup.-10.

[0047] The "oxygen transmissibility", Dk/t, of a lens or material is the
rate at which oxygen will pass through a specific lens or material with
an average thickness of t [in units of mm] over the area being measured.
Oxygen transmissibility is conventionally expressed in units of
barrers/mm, where "barrers/mm" is defined as [(cm.sup.3
oxygen)/(cm.sup.2)(sec)(mm Hg)].times.10.sup.-9.

[0048] The "ion permeability" through a lens correlates with the Ionoflux
Diffusion Coefficient, D (in units of [mm.sup.2/min]), which is
determined by applying Fick's law as follows:

[0049] Described herein are methods for increasing the ion permeability of
an ophthalmic lens. The invention is partly based on unexpected discovery
that by adding a small percentage of an IP-enhancing vinylic monomer or
macromer into silicone hydrogel lens formulations, the ion permeability
of resultant silicone hydrogel contact lenses can be increased
significantly while the water content and the oxygen permeability of the
lenses are not significantly changed, i.e., the changes in water content
or oxygen permeability (Dk) is less than about 8% relative to control
(change in water content over the water content of the control lens or
change in Dk over the Dk value of the control lens).

[0050] In one aspect, the method for increasing the ion permeability of a
silicone hydrogel contact lens comprises: [0051] a. introducing into a
mold a lens-forming material, wherein the lens-forming material comprises
(i) at least one silicone-containing vinylic monomer or macromer, (ii) at
least one hydrophilic vinylic monomer; and (iii) at least one
IP-enhancing vinylic monomer or macromer represented by formula I;

##STR00004##

[0052] wherein X.sup.1 is a direct bond, an oxygen atom

##STR00005##

wherein R' is H or C.sub.1-C.sub.4 alkyl;

[0053] L is a direct bond, a linear or branched C.sub.1-C.sub.10 alkylene
divalent radical (or so-called divalent aliphatic hydrocarbon radical),
or a divalent radical of --X.sup.3-E-X.sup.4--, wherein X.sup.3 and
X.sup.4 are, independently, a linkage selected from the group consisting
of

##STR00006##

[0054] E is an alkylene divalent radical, a cycloalkyl diradical, an
alkylcycloalkyl diradical, an alkylaryl diradical, or an aryl diradical
with up to 40 carbon atoms, wherein E optionally can have ether, thio, or
amine linkages in the main chain;

[0055] Y is
--(R.sup.1--O).sub.n--(R.sup.2--O).sub.m--(R.sup.3--O).sub.p--R wherein
R.sup.1, R.sup.2, and R.sup.3 are, independently, a linear or branched
C.sub.2-C.sub.4-alkylene, and n, m and p are, independently, a number
from 0 to 100, wherein the sum of (n+m+p) is 2 to 100, and R is hydrogen,
a C.sub.1-C.sub.4 alkyl or alkoxy radical, and Z is hydrogen or methyl,

[0056] wherein the silicone hydrogel contact lens obtained by cast-molding
of the lens-forming material with the IP-enhancing vinylic monomer or
macromer of the formula I has an increased ion permeability compared to a
control lens produced from a control lens-forming material without the
IP-enhancing vinylic monomer or macromer of the formula I, [0057] b.
curing the lens-forming material to produce the lens; and [0058] c.
removing the lens from the mold.

[0059] One or more compounds of the formula I can be added in the lens
forming material to produce a silicone hydrogel contact lens with
increased ion permeability. The contact lens has an increased ion
permeability compared to the control lens produced from a control
formulation without a compound of the formula I (having identical
concentrations of all polymerizable components except the compound of
formula I). For example, a lens produced from a lens forming material
including a compound having the formula I has an ion permeability that is
20%, 30%, 40%, 50%, or 60% greater than the control lens. In one aspect,
the ophthalmic lenses produced herein have an Ionoflux Diffusion
Coefficient (D) of at least about 1.5.times.10.sup.-5 mm.sup.2/min,
preferably at least about 2.5.times.10.sup.-5 mm.sup.2/min, and even more
preferably at least about 6.0.times.10.sup.-5 mm.sup.2/min.

[0060] In accordance with the invention, the IP-enhancing vinylic monomer
or macromer of the formula I has a hydrophilic group Y. The hydrophilic
group includes a polyethylene glycol chain or a copolymer chain composed
of ethylene oxide and propylene oxide units, or other hydrophilic
polymers known in the art such as polyvinylpyrrolidone,
polydimethaylacrylamide (PDMA), etc. The molecular weight of the
hydrophilic group can vary as well. In one aspect, the polyalkylene oxide
can have a molecular weight of 100 to 10,000, more preferably 200 to
5,000, and even more preferably 500 to 2,500. In another aspect, Y in
formula I is a residue of polyethylene glycol having a molecular weight
of 500 to 2,500, and Z is methyl.

[0061] In some aspects, two or more compounds having the formula I can be
used to produce the lens. For example, two different compounds having the
formula I can be used, where the hydrophilic group Y are the same group
but each having a different molecular weight. In one aspect, two
compounds having the formula I are used, where for each compound, Z is
methyl, and Y comprises a residue of polyethylene glycol having a
molecular weight of 500 to 2,500, wherein the molecular weight of the
polyethylene glycol residue for each compound is different. For example,
when Y is polyethylene glycol, the molecular weight of polyethylene
glycol in the first compound is 1,100 and the molecular weight of
polyethylene glycol in the second compound is 2,080.

[0062] Compounds of formula I can be obtained from commercial sources or
can be prepared according to any procedures known to a person skilled in
the art. For example, a compound of formula I can be obtained by reacting
a monofunctional terminated polyethylene glycol having one first
functional group selected from the group consisting of isocyanate, amino,
epoxy, hydroxyl, acid chloride, azlactone, and thiol with a vinylic
monomer having a second functional group coreactive with the first
functional group and selected from the group consisting of isocyanate,
amino, epoxy, hydroxyl, acid chloride, azlactone, and thiol group.

[0063] Various monofunctional terminated PEGs can be obtained from
commercial vendors. Preferred monofunctional-terminated PEGs are those
PEGs with one amino, hydroxyl, acid chloride, or epoxy group at one
terminus and a methoxy or ethoxy group at the other terminus.

[0064] The amount of the compound having the formula I used in the methods
described herein can vary depending upon the identity and molecular
weight of the hydrophilic group, the lens-forming materials selected, and
the desired ion permeability. In one aspect, the amount of the compound
having the formula I is up to about 3% by weight, preferably from about
0.5% to about 2.5% by weight in the lens formulation.

[0065] The compound having the formula I is polymerized with other
lens-forming materials to produce an ophthalmic lens. The lens-forming
material can be a polymerizable fluid that includes, for example, a
solution, a dispersion, a solvent-free liquid, or a melt at a temperature
below 60.degree. C. In some aspects, the lens-forming material includes,
but is not limited to, an actinically crosslinkable prepolymer.

[0069] A class of preferred silicone-containing vinylic monomers or
macromers is polysiloxane-containing vinylic monomers or macromers. A
"polysiloxane-containing vinylic monomer or macromer" refers to a vinylic
monomer or macromer containing at least one ehtylenically unsaturated
group and a divalent radical of

[0070] Another class of preferred silicone-containing macromers is
silicon-containing prepolymers comprising hydrophilic segments and
hydrophobic segments. Any suitable silicone-containing prepolymers with
hydrophilic segments and hydrophobic segments can be used herein.
Examples of such silicone-containing prepolymers include those described
in commonly-owned U.S. Pat. Nos. 6,039,913, 7,091,283, 7,268,189 and
7,238,750, 7,521,519; commonly-owned US patent application publication
Nos. US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US
2008-0234457 A1, US 2008-0231798 A1, and commonly-owned U.S. patent
application Nos. 61/180,449 and 61/180,453; all of which are incorporated
herein by references in their entireties.

[0072] A polymerizable composition for making silicone hydrogel lenses can
also comprise one or more crosslinking agents (i.e., compounds with two
or more acryl groups or three or more thiol or ene-containing groups and
with molecular weight less than 700 Daltons). Examples of preferred
cross-linking agents include without limitation tetraethyleneglycol
diacrylate, triethyleneglycol diacrylate, ethyleneglycol diacylate,
diethyleneglycol diacrylate, tetraethyleneglycol dimethacrylate,
triethyleneglycol dimethacrylate, ethyleneglycol dimethacylate,
diethyleneglycol dimethacrylate, trimethylopropane trimethacrylate,
pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl
methacrylate, ethylenediamine dimethyacrylamide, ethylenediamine
diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl
cyanurate, allylmethacrylate, allylmethacrylate,
1,3-bis(methacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane-
, N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide,
N,N'-ethylenebisacrylamide,
N,N'-ethylenebismethacrylamide,1,3-bis(N-methacrylamidopropyl)-1,1,3,3-te-
trakis-(trimethylsiloxy)disiloxane,
1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane-
, 1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,
1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)d-
isiloxane, and combinations thereof. A preferred cross-linking agent is
tetra(ethyleneglycol) diacrylate, tri(ethyleneglycol) diacrylate,
ethyleneglycol diacrylate, di(ethyleneglycol) diacrylate,
methylenebisacrylamide, triallyl isocyanurate, or triallyl cyanurate. The
amount of a cross-linking agent used is expressed in the weight content
with respect to the total polymer and is preferably in the range from
about 0.05% to about 4%, and more preferably in the range from about 0.1%
to about 2%.

[0073] It must be understood that a polymerizable composition for making
silicone hydrogel lenses can also comprise various components, such as,
for example, polymerization initiators (e.g., photoinitiator or thermal
initiator), a visibility tinting agent (e.g., dyes, pigments, or mixtures
thereof), a polymerizable UV-absorbing agent, a polymerizable latent
UV-absorbing agent, antimicrobial agents (e.g., preferably silver
nanoparticles), bioactive agent, leachable lubricants, and the like, as
known to a person skilled in the art.

[0074] Examples of suitable photoinitiators include, but are not limited
to, benzoin methyl ether, diethoxyacetophenone, a benzoylphosphine oxide,
1-hydroxycyclohexylphenyl ketone, or Darocure.RTM. or Irgacure.RTM.
types, for example Darocure.RTM. 1173 or Irgacure.RTM. 2959. Examples of
benzoylphosphine initiators include
2,4,6-tri-methylbenzoyldiphenylophosphine oxide, bis-(2,6
dichlorobenzoyl)-4-N-propylphenylphosphine oxide; and
bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. The amount of
photoinitiator can be selected within wide limits, an amount of up to
0.05 g/g of prepolymer and preferably up to 0.003 g/g of prepolymer can
be used. A person skilled in the art will know well how to select the
appropriate photoinitiator. Examples of thermal initiators include, but
are not limited to, 2,2'-azobis(2,4-dimethylpentanenitrile),
2,2'-azobis(2-methylpropanenitrile), 2,2'-azobis(2-methylbutanenitrile),
azobisisobutyronitrile (AIBN), peroxides such as benzoyl peroxide, and
the like.

[0075] In some aspects, the lens-forming material can further include a
UV-absorber, a tinting agent, an antimicrobial agent, an inhibitor, a
filler or any combination thereof. In one aspect, the ultraviolet
absorber can include, for example, a benzotriazole or a benzophenone.
Many benzotriazole and benzophenone IN absorbers are known and many are
commercially available. The identity of the benzotriazole or benzophenone
UV absorber is not critical, but should be selected based on its
characteristic UV cut-off to give the desired UV absorbing property.

[0076] In general, the lens-forming materials and other components are
mixed together in a solvent prior to introduction into the mold. Examples
of suitable solvents are water, alcohols (e.g., lower alkanols having up
to 6 carbon atoms, such as ethanol, methanol, propanol, isopropanol),
carboxylic acid amides (e.g., dimethylformamide), dipolar aprotic
solvents (e.g., dimethyl sulfoxide or methyl ethyl ketone), ketones
(acetone or cyclohexanone), hydrocarbons (e.g., toluene), ethers (e.g.,
THF, dimethoxyethane or dioxane), and halogenated hydrocarbons (e.g.,
trichloroethane), and any combination thereof. The use of water alone or
in combination with other solvents can be used herein. For example, the
aqueous solution of the lens-forming materials can also include, for
example an alcohol, such as methanol, ethanol or n- or iso-propanol, or a
carboxylic acid amide, such as N,N-dimethylformamide, or dimethyl
sulfoxide. In one aspect, the aqueous solution of the lens-forming
materials contains no further solvent.

[0077] In some aspects, the lens-forming material as described above is
poured into a mold with a specific shape and size. When the ocular device
is a contact lens, the lens can be produced using techniques known in the
art. For example, the contact lens can be produced in a conventional
"spin-casting mold," as described for example in U.S. Pat. No. 3,408,429,
or by the full cast-molding process in a static form, as described in
U.S. Pat. Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810.

[0078] Lens molds for making contact lenses are well known in the art. For
example, a mold (for full cast molding) generally comprises at least two
mold sections (or portions) or mold halves, i.e. first and second mold
halves. The first mold half defines a first molding (or optical) surface
and the second mold half defines a second molding (or optical) surface.
The first and second mold halves are configured to receive each other
such that a lens forming cavity is formed between the first molding
surface and the second molding surface. The molding surface of a mold
half is the cavity-forming surface of the mold and in direct contact with
the lens-forming material.

[0079] Methods of manufacturing mold sections for cast-molding a contact
lens are generally well known to those of ordinary skill in the art. The
first and second mold halves can be formed through various techniques,
such as injection molding or lathing. Examples of suitable processes for
forming the mold halves are disclosed in U.S. Pat. Nos. 4,444,711;
4,460,534; 5,843,346; and 5,894,002, which are also incorporated herein
by reference.

[0080] Virtually all materials known in the art for making molds can be
used to make molds for preparing ocular lenses. For example, polymeric
materials, such as polyethylene, polypropylene, polystyrene, PMMA, cyclic
olefin copolymers (e.g., Topas.RTM. COC from Ticona GmbH of Frankfurt,
Germany and Summit, N.J.; Zeonex.RTM. and Zeonor.RTM. from Zeon Chemicals
LP, Louisville, Ky.), or the like can be used. Other materials that allow
UV light transmission could be used, such as quartz glass and sapphire.

[0081] Once the lens-forming material is poured into the mold, the
lens-forming material is cured (i.e., polymerized) to produce a polymeric
matrix and ultimately the lens. The techniques for conducting the
polymerization step will vary depending upon the selection of the
lens-forming material. In one aspect, when the lens-forming material
comprises a prepolymer comprising one or more actinically-crosslinkable
ethylenically unsaturated groups, the mold containing the admixture can
be exposed to a spatial limitation of actinic radiation to polymerize the
prepolymer. In other aspects, the mold containing the lens forming
material can be subjected to heat in order to cure the lens-forming
material.

[0082] In other aspects, the energy used to cure the lens-forming material
is in the form of rays directed by, for example, a mask or screen or
combinations thereof, to impinge, in a spatially restricted manner, onto
an area having a well defined peripheral boundary. For example, a spatial
limitation of UV radiation can be achieved by using a mask or screen that
has a transparent or open region (unmasked region) surrounded by a UV
impermeable region (masked region), as schematically illustrated in FIGS.
1-9 of U.S. Pat. No. 6,627,124 (herein incorporated by reference in its
entirety). The unmasked region has a well defined peripheral boundary
with the unmasked region. The energy used for the crosslinking is
radiation energy, UV radiation, visible light, gamma radiation, electron
radiation or thermal radiation, the radiation energy preferably being in
the form of a substantially parallel beam in order on the one hand to
achieve good restriction and on the other hand efficient use of the
energy.

[0083] In one aspect, the mold containing the lens-forming material is
exposed to light having a wavelength greater than 300 nm, greater than
310 nm, greater than 320 nm, greater than 330 nm, greater than 340 nm,
greater than 350 nm, greater than 360 nm, greater than 370 nm, or greater
than 380 nm. Cut-off filters known in the art can be used to filter and
prevent specific wavelengths of energy from contacting the mold and
lens-forming material. The time the lens-forming mixture is exposed to
the energy is relatively short, e.g. in less than or equal to 150
minutes, in less than or equal to 90 minutes, in less than or equal 60
minutes, less than or equal to 20 minutes, less than or equal to 10
minutes, less than or equal to 5 minutes, from 1 to 60 seconds, or from 1
to 30 seconds.

[0084] The methods described herein increase the ion permeability of an
ophthalmic lens without adversely affecting other properties of the lens.
For example, as demonstrated in the Examples, the lens' water content and
oxygen permeability remain essentially the same when one or more
compounds having the formula I are used to produce the lens vs. the
control lens without a compound having the formula I. In one aspect, the
lens has a water content from 30% to 37%. In another aspect, the lens has
an oxygen permeability greater than 70. Additionally, the use of
compounds having the formula I result in the formation of clear lenses,
which is another important feature. In one aspect, depending on the
composition of the silicone hydrogel formulation, the preferred water
content of the lens is from 20% to 50%, with an oxygen permeability
greater than 70.

EXAMPLES

[0085] The following examples are put forth so as to provide those of
ordinary skill in the art with a complete disclosure and description of
how the compounds, compositions, and methods described and claimed herein
are made and evaluated, and are intended to be purely exemplary and are
not intended to limit the scope of what the inventors regard as their
invention. Efforts have been made to ensure accuracy with respect to
numbers (e.g., amounts, temperature, etc.) but some errors and deviations
should be accounted for. Unless indicated otherwise, parts are parts by
weight, temperature is in .degree. C. or is at ambient temperature, and
pressure is at or near atmospheric. There are numerous variations and
combinations of reaction conditions, e.g., component concentrations,
desired solvents, solvent mixtures, temperatures, pressures and other
reaction ranges and conditions that can be used to optimize the product
purity and yield obtained from the described process. Only reasonable and
routine experimentation will be required to optimize such process
conditions.

[0086] Oxygen permeability measurements. The oxygen permeability of a lens
and oxygen transmissibility of a lens material is determined according to
a technique similar to the one described in U.S. Pat. No. 5,760,100 and
in an article by Winterton et al., (The Cornea: Transactions of the World
Congress on the Cornea 111, H.D. Cavanagh Ed., Raven Press: New York
1988, pp 273-280), both of which are herein incorporated by reference in
their entireties. Oxygen fluxes (J) are measured at 34.degree. C. in a
wet cell (i.e., gas streams are maintained at about 100% relative
humidity) using a Dk1000 instrument (available from Applied Design and
Development Co., Norcross, Ga.), or similar analytical instrument. An air
stream, having a known percentage of oxygen (e.g., 21%), is passed across
one side of the lens at a rate of about 10 to 20 cm.sup.3/min., while a
nitrogen stream is passed on the opposite side of the lens at a rate of
about 10 to 20 cm.sup.3/min. A sample is equilibrated in a test media
(i.e., saline or distilled water) at the prescribed test temperature for
at least 30 minutes prior to measurement but not more than 45 minutes.
Any test media used as the overlayer is equilibrated at the prescribed
test temperature for at least 30 minutes prior to measurement but not
more than 45 minutes. The stir motor's speed is set to 1200.+-.50 rpm,
corresponding to an indicated setting of 400.+-.15 on the stepper motor
controller. The barometric pressure surrounding the system,
P.sub.measured, is measured. The thickness (t) of the lens in the area
being exposed for testing is determined by measuring about 10 locations
with a Mitotoya micrometer VL-50, or similar instrument, and averaging
the measurements. The oxygen concentration in the nitrogen stream (i.e.,
oxygen which diffuses through the lens) is measured using the DK1000
instrument. The apparent oxygen permeability of the lens material,
Dk.sub.app, is determined from the following formula:

[0093] The oxygen transmissibility (Dk/t) of the material may be
calculated by dividing the oxygen permeability (Dk.sub.app) by the
average thickness (t) of the lens.

[0094] Ion Permeability Measurements. The ion permeability of a lens is
measured according to procedures described in U.S. Pat. No. 5,760,100
(herein incorporated by reference in its entirety. The values of ion
permeability reported in the following examples are relative ionoflux
diffusion coefficients (D/D.sub.ref) in reference to a lens material,
Alsacon, as reference material. Alsacon has an ionoflux diffusion
coefficient of 0.314.times.10.sup.-3 mm.sup.2/minute.

[0096] Formulation A is made by the following procedure. For lightstream
(LS) lens casting, L-PEG-2000 and 1-propanol are mixed first. After
vortexing for 3 minutes in the Mini Vortexer, CE-PDMS, TRIS-MA, DMA and
Darocur 1173 are added. For DSM lens casting, no L-PEG-2000 is used in
the formulation. The bottle is placed on a roller (model No LJRM, PAULO
ABBE) and rolled slowly for about 2 hours before the formulation is used
for making lenses.

Example 2

Preparation of Silicone Hydrogel Contact Lens from Formulation A with
PEG-MA

[0097] Formulation A modified with PEG additives is studied. Experiments
are carried out to study the maximum percentage of polyethylene glycol
methacrylate (PEG-MA) or PEG-MA mixture having different molecular
weights that can be incorporated into formulation A while still achieving
clear lenses. PEG-MA 2080 (Mw 2080, 50% in water) and PEG-MA 1100 are
purchased from Aldrich-Sigma and used as received. The composition of the
lens formulations are shown in Table 1. Lenses are prepared by using the
full-cast molding of a lens formulation in polypropylene molds under UV
irradiation (Philips F20T12 bulb, an intensity of 5.4 mW/cm.sup.2
(measured by IL 1700 radiometer), curing time is 10 min).

[0098] The following additives are evaluated (Table 1): (1)
PEG-MA2080/H.sub.2O at 0.5% or 0.75% when using 1-propanol as solvent.
(2) Mixtures: a: 0.5% PEG-MA 2080/H.sub.2O and 2% PEG-MA1100; b: 0.75%
PEG-MA 2080/H.sub.2O and 1% PEG-MA1100; c: 0.75% PEG-MA 2080/H.sub.2O and
1% PEG-MA526. At 0.75%, the freeze dried PEG-MA2080 leads to cloudy
formulation. The formulation can be cleared up by warming up to
50.degree. C., but the lenses are still cloudy.

[0099] Some clear formulations, as listed in Table 2, are chosen for a
more detailed study of lens properties. An unexpected high ion
permeability (IP) value of above 10 for lenses produced with the PEG
additive is observed. A control lens without PEG-MA is made and had an IP
value of 4.9.

The Dk values are similar between lenses with or without PEG additives.

[0100] Contact lenses with high IP can be obtained from a lens formulation
including a PEG additive using double sided molding (DSM) process. As
listed in Table 3, unexpected high IP values are also observed for the
lenses cured by the DSM curing process using poly(cycloalkylenedialkylene
terephthalate) (PCTA) molds at a light intensity of 5.4 mW/cm.sup.2
(measured by IL1700 radiometer) with Philips F20T12 bulb for about 10
minutes. Lens formulations (formulation A) containing 0.75% PEG-MA2080 or
1% PEG-MA1100+0.75% PEG-MA2080, yielded much higher IP values.

[0101] Formulation B is prepared by using the same procedure as
formulation A, except that the TRIS-methacrylamide used in formulation A
is replaced with TRIS-acrylamide in formulation B. Lenses with PEG
additives are made from formulation B with one or two additives: 0.75%
PEG-MA2080 and 0.75% PEG-MA2080 plus 1%E0-PO-MA. EO-PO is a copolymer of
ethylene oxide and propylene oxide. The IP value increased from about 8.7
(control-no PEG) to 13.1 or 15.1 (with PEG), while the Dk remained
unchanged.

[0103] The compatibility of PEG-MA is investigated. The lenses are made by
DSM curing process using PP molds. IP values are provided in Table 5.
1.5% and 2% PEG-MA2080 resulted in the formation of cloudy formulations C
and D. If PEG-MA1100 is used in formulations C and D, the maximum
percentage amount of PEG additive that can be used before the formulation
becomes cloudy is 10% and 13.8%, respectively. If the mixture of
PEG-MA2080 and PEG-MA1100 is used, when 0.75% PEG-MA2080 is used, it is
desirable that the percentage of PEG-MA1100 not be higher than 8% in
either of formulations C and D.

[0104] In this example, the impact of PEG additive on IP values is studied
using lenses coated with methane-air rotary plasma coating. As shown in
Table 6, except for one condition, IP values increased for lenses with
the PEG additive. The IP value increase is statistically significant at
95% confidence level (based on one-way ANOVA analysis).

[0105] In this example, the impact of PEG additive on IP value is studied
using lenses coated with methane-air linear plasma coating or
methane-nitrogen linear plasma coating. As listed in Table 7 and Table 8,
IP values increased for lenses having PEG additive. For most of the
conditions, the IP value increase is statistically significant at 95%
confidence level.

[0106] Throughout this application, various publications are referenced.
The disclosures of these publications in their entireties are hereby
incorporated by reference into this application in order to more fully
describe the compounds, compositions and methods described herein.

[0107] Various modifications and variations can be made to the compounds,
compositions and methods described herein. Other aspects of the
compounds, compositions and methods described herein will be apparent
from consideration of the specification and practice of the compounds,
compositions and methods disclosed herein. It is intended that the
specification and examples be considered as exemplary.